Compositions and methods for delivery of riboflavin

Abstract

Methods of treating eyes are described. The method may include administering an agent capable of disrupting corneal cell junctures to a corneal surface of the eye, the corneal surface comprising an intact epithelium and stroma; and administering riboflavin to the corneal surface after or simultaneously with the agent. The riboflavin may diffuse through the eye to penetrate the stroma within 10 minutes of administration of the riboflavin.

1 . A method of treating an eye of a subject, the method comprising:
 administering an agent capable of disrupting corneal cell junctures to a corneal surface of the eye, the corneal surface comprising an intact epithelium and stroma; and   administering a therapeutically-effective amount of riboflavin to the corneal surface after or simultaneously with the agent;   wherein the riboflavin diffuses through the eye to penetrate the stroma within 10 minutes after administering the riboflavin.   
     
     
         2 . The method of  claim 1 , wherein administering the agent to the corneal surface includes contacting the corneal surface with a buffered solution comprising the agent for at least 30 seconds. 
     
     
         3 . The method of  claim 2 , wherein the solution is administered using an applicator placed against the corneal surface. 
     
     
         4 . The method of  claim 2 , wherein the solution comprises the therapeutically-effective amount of riboflavin. 
     
     
         5 . The method of  claim 1 , wherein the therapeutically-effective amount of riboflavin is administered within 5 minutes after administering the agent. 
     
     
         6 . The method of  claim 1 , wherein the agent comprises an anhydride, an acid chloride, a sulfonyl chloride, or a sulfonic acid. 
     
     
         7 . The method of  claim 1 , further comprising administering a buffer solution or physiological saline solution to the corneal surface before administering the agent to deprotonate free amines on corneal proteins. 
     
     
         8 . The method of  claim 7 , wherein the buffer solution or physiological saline solution has a concentration ranging from 0.05 M to 1.0 M. 
     
     
         9 . The method of  claim 2 , wherein the solution has a pH of from 7.5-9.0. 
     
     
         10 . The method of  claim 2 , wherein the solution comprises dibasic sodium phosphate, monobasic sodium phosphate, disodium phosphate, or a mixture thereof. 
     
     
         11 . The method of  claim 2 , wherein the solution has a concentration of the agent ranging from about 1.0 mg/mL to about 5.0 mg/mL. 
     
     
         12 . The method of  claim 1 , wherein the agent dissociates molecular bridges between stromal collagen fibers. 
     
     
         13 . The method of  claim 1 , wherein the therapeutically-effective amount of riboflavin is administered as a solution having a concentration of about 0.5 mg/mL to about 5.0 mg/mL riboflavin, the solution comprising riboflavin being the same or different than the solution comprising the agent. 
     
     
         14 . The method of  claim 1 , wherein the therapeutically-effective amount of riboflavin is administered to the corneal surface by a plurality of drops. 
     
     
         15 . The method of  claim 1 , wherein the therapeutically-effective amount of riboflavin corresponds to a total volume of riboflavin in solution ranging from about 0.1 mL to about 1.0 mL. 
     
     
         16 . The method of  claim 1 , wherein at least 50% of the therapeutically-effective amount of riboflavin administered to the corneal surface diffuses into the stroma within 5 minutes of administering the riboflavin. 
     
     
         17 . The method of  claim 1 , wherein at least 75% of the therapeutically-effective amount of riboflavin administered to the corneal surface diffuses into the stroma within 5 minutes of administering the therapeutically-effective amount of riboflavin. 
     
     
         18 . The method of  claim 1 , wherein at least 90% of the therapeutically-effective amount of riboflavin administered to the corneal surface diffuses into the stroma within 5 minutes of administering the therapeutically-effective amount of riboflavin. 
     
     
         19 . The method of  claim 1 , wherein at least 75% of the therapeutically-effective amount of riboflavin administered to the corneal surface diffuses into the stroma within 2 minutes of administering the therapeutically-effective amount of riboflavin. 
     
     
         20 . The method of  claim 1 , further comprising irradiating the eye with UVA light.